Given their small size, flaviviruses are a good model system for understanding the role of intrinsically disordered protein regions in viral function. Finally, studying these viruses disordered protein regions will certainly contribute to the development of therapeutic approaches against such promising (yet challenging) targets. The potential health risks of cannabis are of growing concern, including effects on reproduction and development. Extensive research has investigated risks associated with maternal exposure to THC during gestation and its impacts on the development of offspring, but little research has been done regarding paternal THC exposure effects prior to conception. We have previously found that paternal THC exposure in rats causes changes in sperm methylation. In an initial study we also showed that a 12-day paternal THC exposure prior to conception alters locomotor activity and impairs cognitive function of their offspring. This study investigated the cross-generational effects of chronic paternal THC exposure in rats (0, 2, or 4 mg/kg/day SC for 28 days) prior to mating with drug naïve females. The offspring of THC-exposed male rats had significant alterations in locomotor activity and cognitive function. Specifically, during adolescence there was significant locomotor hyperactivity in the offspring of males exposed to 2 mg/kg/day of THC. During the novel object recognition task, the controls maintained their relative preference for the novel object across the duration of the ten-min session while the rats whose fathers received THC (2 mg/kg/day) showed a significantly greater drop-off in interest in the novel object during the second half of the session. Learning in the radial-arm maze was significantly delayed in the offspring of males exposed to 4 mg/kg/day of THC. This study shows that premating chronic paternal THC exposure at multiple dose regimens can cause long-lasting detrimental behavioral effects in their offspring, including abnormal locomotor activity and impaired cognitive function. Future studies should investigate the underlying mechanisms driving these aberrant developmental outcomes and seek to identify possible treatments of alleviation in the presence of paternal THC exposure. n-Hexane has been reported to induce serious peripheral neuropathy in workers. Pyrrole adducts are the unique reaction products of n-hexane in organisms and have been demonstrated to be critical to n-hexane neuropathy. Our previous studies have demonstrated that pyrrole adducts could accumulate in hair and showed high correlation with neuropathy at the end of experiments in rat models. In the present study, we examined the time course of hair pyrrole adducts and behavioral changes in rats exposed to different dosages of n-hexane in both treatment (24 weeks) and recovery phases. Our results showed 1. After treatment, 1.0, 2.0, and 4.0 g/kg dosage groups all lost weight, but the 0.5 g/kg dosage group showed no impairment; after recovery, all impaired rats regained weight. 2. After treatment, 1.0, 2.0, and 4.0 g/kg dosage groups all showed a rise in gait scores, decreased rotarod latency, and decreased motor nerve conduction velocity, whereas the 0.5 g/kg dosage group showed no impairment; after recovery, all imsure limit in humans. V.Frailty and cognitive impairment are among the 2 most common geriatric syndromes. Their presence poses major risks to the elderly including greater disability, reduced quality of life, and higher morbi-mortality. Recent evidence suggest that frailty can be a risk factor for incident dementia. The opposite is also true since subjects with Alzheimer’s disease and other dementia also present with more severe frailty measures. The mechanisms for the association between frailty and cognitive impairment is not clear, but possibly involves abnormalities in biological processes related to aging. Here, we will review the current evidence of the association between frailty and cognitive impairment. We will also review the possible biological mechanistic links between the 2 conditions. Finally, we will address potential therapeutic targets and interventions that can mitigate both conditions. The a3 isoform of vacuolar-type proton-pumping ATPase (V-ATPase) is essential for bone resorption by osteoclasts. Although more than 90 mutations of the human a3 gene have been identified in patients with infantile malignant osteopetrosis, it is unclear whether they lead to osteoclast dysfunction. We have established an in vitro assay to induce osteoclasts from spleen macrophages derived from a3-knockout mice. Here, we examined the effects of these mutations in a3-knockout osteoclasts. We were interested in four mutations, two short deletions and two missense mutations, previously identified in the a3 cytosolic domain. a3 harboring either of the two short deletions was hardly expressed in osteoclasts and calcium phosphate resorption was impaired. Epoxomicin in vitro On the other hand, osteoclasts expressing a3 with either of the two missense mutations exhibited no defects. Specifically, expression levels of the mutant proteins, V-ATPase assembly, and calcium phosphate resorption activity were similar to those of the wild type. Moreover, these missense mutants interacted with Rab7, a small GTPase that regulates lysosomal trafficking. These results suggest that the short deletions impair a3 expression and thus disrupt V-ATPase subunit assembly essential for bone resorption, while the missense mutations do not cause osteoclast dysfunction without an additional mutation(s) or impair resorption of bone, but not of calcium phosphate. As standard mathematical models for the transmission of vector-borne pathogens with weak or no apparent sterilizing immunity, Susceptible-Infected-Susceptible (SIS) systems such as the Ross-Macdonald equations are a useful starting point for modeling the impacts of interventions on prevalence for diseases that cannot superinfect their hosts. In particular, they are parameterizable from quantities we can estimate such as the force of infection (FOI), the rate of natural recovery from a single infection, the treatment rate, and the rate of demographic turnover. However, malaria parasites can superinfect their host which has the effect of increasing the duration of infection before total recovery. Queueing theory has been applied to capture this behavior, but a problem with current queueing models is the exclusion of factors such as demographic turnover and treatment. These factors in particular can affect the entire shape of the distribution of the multiplicity of infection (MOI) generated by the superinfection process, its transient dynamics, and the population mean recovery rate.